The aortic pressure waveform results from a coupling of cardiac and vascular functions. The combined effects form a waveform shape that reflects the status of the cardiovascular system. The size and shape of the aortic pulse is affected by cardiac output, arterial stiffness and left ventricular (LV) function. Measuring aortic pressure will provide a useful diagnostic tool to the cardiovascular system. The only direct method to measure aortic pressure is through an invasive procedure, which includes inserting a catheter with either a pressure sensor on the tip or a fluid-filled catheter connected to an external pressure sensor located on the electronic module. The method not only increases the risk to the patient, but is cumbersome, intrusive, and a time-consuming procedure that requires significant use of hospital facilities and staff.
A non-invasive and easy alternative is to use a conventional blood pressure cuff sphygmomanometer or any equivalent electronic device to measure the brachial pressure as an indicator for aortic pressure and cardiovascular risk. However, this measurement disregards basic cardiovascular hemodynamic principles: that the pressure waveform amplifies and changes in shape as it travels from the aorta to brachial artery. The changes are due to the difference in arterial properties between the two arterial locations and the influence of wave reflections in the arterial tree. See, Wilmer Nichols, Michael O'Rourke, McDonald's Blood Flow In Arteries: Theoretical, Experimentation and Clinical Principles, 5th Edition, Hodder Arnold, 2005. As a result, the brachial systolic pressure is exaggerated compared to that in the ascending aorta and, therefore, not indicative of cardiac afterload. The consequence of this difference in systolic pressure is demonstrated in numerous studies in which brachial pressure is not indicative of cardiovascular risk when compared to aortic pressure. See, Mary J. Roman, Richard B. Devereux, Jorge R. Kizer, Peter M. Okin, Elisa T. Lee, PHD, Wenyu Wang, Jason G. Umans, Darren Calhoun, Barbara V. Howard, High Central Pulse Pressure Is Independently Associated With Adverse Cardiovascular Outcome: The Strong Heart Study J Am Coll Cardiol 2009; 54:1730-4; and Carmel M. McEniery, Yasmin, Barry McDonnell, Margaret Munnery, Sharon M. Wallace, Chloe V. Rowe, John R. Cockcroft, Ian B. Wilkinson, Central Pressure: Variability and Impact of Cardiovascular Risk Factors: The Anglo-Cardiff Collaborative Trial II Hypertension. 2008; 51:1-7. This difference is also important in the treatment of hypertension since different classes of anti-hypertensive drugs, for the same reduction in brachial systolic pressure, show substantial differences in reduction of central systolic pressure. See, Bryan Williams, Peter S. Lacy, Simon M. Thom, Kennedy Cruickshank, Alice Stanton, David Collier, Alun D. Hughes, H. Thurston, Differential Impact of Blood Pressure-Lowering Drugs on Central Aortic Pressure and Clinical Outcomes Principal Results of the Conduit Artery Function Evaluation (CAFE) Study Circulation. 2006; 113:1213-1225. Furthermore, traditional cuff brachial blood pressure devices do not measure the pressure waveform. The pressure waveform, especially the ascending aortic waveform, provides the physician insight into cardiovascular function, load and arterial stiffness not available from just brachial measurement of systolic and diastolic pressures.
The most common arterial site used as a surrogate to the aorta is the carotid artery. The carotid pressure waveform is similar in shape to the aortic pressure waveform given the carotid artery proximity to the aorta. A tonometer can be used to measure the carotid pressure non-invasively. However, it is technically difficult to record a high fidelity carotid pulse since the carotid location does not meet a number of the requirements for tonometric recordings (1). Thus, a high level of operator skill is required to obtain accurate carotid waveforms. In addition, the measured carotid waveform needs calibration, usually from a cuff blood pressure measurement on the brachial artery. Given that the brachial systolic pressure (SP) is different than the carotid SP and that both mean and diastolic pressure (MP and DP) is the same throughout the large, conduit arteries, the carotid pulse require measured brachial MP and DP to be calibrated. Since MP is not usually provided by conventional BP devices, MP is often estimated using an approximation equation using brachial SP and DP only ignoring the different shape and length of brachial pressure pulses. An accurate measure of brachial MP requires averaging the brachial pressure waveform where MP is dependent on contour of the pulse, not just its height. Hence an equation to estimate MP based only on pulse height may not produce an accurate value of MP. This would introduce error into the carotid pulse calibration so that the carotid pulse would not be an accurate measure of the aortic pressure.
Consequently, other non-invasive methods have been introduced, most prominently a method comprised of calculating the aortic pressure waveform from a noninvasive radial pressure tonometer measured waveform using a general transfer function representing the upper arm arterial system which does not change with age or gender, See O'Rourke U.S. Pat. No. 5,265,011. The transfer function represents the ratio of harmonics amplitude and phase of aortic to radial pressure waveforms. This method validated by the FDA had been implemented commercially and has been proved to be an accurate non-invasive method of estimating aortic pressure. See, Alfredo L. Pauca, Michael F. O'Rourke, Neal D. Kon, Prospective Evaluation of a Method for Estimating Ascending Aortic Pressure From the Radial Artery Pressure Waveform, Hypertension. 2001; 38:932-937; and James E. Sharman, Richard Lim, Ahmad M. Qasem, Jeff S. Coombes, Malcolm I. Burgess, Jeff Franco, Paul Garrahy, Ian B. Wilkinson, Thomas H. Marwick, Validation of a Generalized Transfer Function to Noninvasively Derive Central Blood Pressure During Exercise. Hypertension. 2006; 47:1203-1208. The proposed invention differs from this method by the use of a brachial cuff, which is similar to the one used in conventional cuff blood pressure measurement device, to derive the aortic pressure waveform instead of tonometer. Another advantage of the proposed invention is in the use on subjects with a fistula whose radial signal is undetectable.
Although the patent by O'Rourke (U.S. Pat. No. 5,265,011) proposed a general brachial to aortic pressure transfer function based on harmonics ratio to calculate aortic pressure, such a transfer function applies only to the brachial pressure waveform, not brachial arterial volume displacement waveform measured by a cuff. The volume waveform shape differs and is more dependent upon the cuff inflation pressure than the pressure waveform. This can lead to substantial differences in the shape of the two waveforms and, in turn, inaccurate measures of the mean pressure and characteristic waveform parameters. Furthermore, the O'Rourke patent did not address methods of obtaining the brachial pressure waveform non-invasively or the issues of using a surrogate easy-to-use, operator independent measurement for the brachial pulse. The proposed invention address these issues providing an easy to use method with appropriate transfer function or mathematical transformation for a brachial cuff volume waveform based on the cuff pressure.
A recent European patent application by Chen and Cheng (EP 2070472A1) discloses an oscillometric cuff volume waveform on the brachial artery to determine central aortic pressure using multi-regression analysis. The procedure accordingly requires recording oscillometric cuff volume waveform similar to the one used in electronic manometer blood pressure devices. The method requires that the cuff pulse be recorded after the cuff pressure is decreasing to a certain degree and during re-increasing of the cuff pressure. Second, the recorded cuff volume waveform is calibrated by mean and diastolic pressure. The patent mentions, in general, different methods based on multiple regression analysis to calculate central aortic systolic and diastolic pressure. One method uses multiple regression analysis from cuff pulse curve parameters as inputs to determine central systolic pressure.
There are many problems with the method proposed by Chen and Cheng in practice and theory. The method ignores the fact that the cuff volume waveforms morphology change depending on the difference between the cuff pressure and the subject's blood pressure, and not on the absolute value of the cuff pressure as proposed in that patent. Such differences would affect the brachial vascular unloading and cause changes in the pulse wave shape and size. This method does not indicate specifically the range of cuff pressures needed for recording a valid volume pulse. Without specifying that range of cuff pressures, the cuff volume waveform will have a different size and shape at different cuff pressure values. These differences in size and shape would, in turn, vary the cuff volume waveform parameters which are used to calculate central pressure. In some cases, these cuff waveform features used in the regression equation like second shoulder couldn't be identified. Furthermore regression equation accuracy and variation is dependent on the accuracy and variation of its parameters. Hence, central pressure estimated using the regression equation is susceptible to errors and variations in its many input parameters. These errors consequently affect the stability, consistency, and accuracy of the result.
Another patent application (US 2009/0287097 A1) by Lowe to calculate aortic pressure from a cuff volume waveform addresses the effect of the cuff pressure on the oscillometric cuff volume waveform. To stabilize the cuff volume waveform, the method proposes increasing the cuff pressure above systolic pressure by 25 mmHg, called suprasystolic pressure, and recording the cuff volume waveform. Through a series of assumptions regarding the changes in arterial diameter between brachial and subclavian root, an equation is formed that relates the pressure wave at the subclavian root to the brachial artery. The equation proposed to estimate aortic pressure from the measured cuff volume waveform at suprasystolic pressure in the brachial artery requires the assumption of four constants. One constant related to reflection coefficient at the occluded brachial arterial pulse, and another related to the travel time of the wave from the subclavian root to the cuff occlusion. The reconstructed aortic waveform resulting from that equation requires scaling, calibration or correction as a result of the effect of the pressure difference between the cuff and mean pressure and the effect of suprasystolic cuff pressure. As a result the other two constants, based on these factors, are needed to rescale the reconstructed waveform.
Although the method by Lowe is based on reasonable and solid theory, and the method already addresses the stability of the oscillometric cuff pulse by adjusting the cuff pressure above systole, the method suffers from being impractical in application and dependent on many assumptions that affect the accuracy of the aortic pressure estimation. The method requires the knowledge of four constants with no defined means to estimate these constants. It is not known if these constants, especially the two scaling constants, can be generalized to all populations regardless of age, gender, height or weight. In the patent application, these constants were chosen arbitrarily and the author suggested estimating them from an independent set of data determined from invasive recordings or through mathematical modeling ([0076] in Patent application US 2009/0287097 A1). Without such information, the method has limited application and produces erroneous results.
Furthermore, as pulses travel from the aorta to the periphery, the pulses change and amplify. The amplification is, in part, dependent on the pulses' harmonic content at the aorta and in the periphery. One factor that affects the pulse harmonic content is the length of the cardiac pulse, or heart rate. The equation proposed by Lowe to calculate aortic pulse from brachial cuff pulse does not consider the effect of heart rate, and hence, did not consider the harmonic amplification nature of the traveling pulse. For example, it is known through invasive studies and principles of cardiovascular hemodynamics that changes in heart rate alters pulse harmonics and consequently affect the amplification ratio from the aorta to the periphery (1). However, according to equation in Lowe's patent, pressure pulses with the same systolic and diastolic pressure but different heart rates would produce similar aortic pulse results whereas cardiovascular hemodynamics principles teach that the results should be different.
In addition to this fundamental issue, the measurement requires the occlusion of the brachial artery and cessation of the blood flow in the arm until proper waveforms are recorded which would be uncomfortable for the patient.
Another patent by Wasserttheuer WO 2007/053868, (PCT/AT2006/000457) proposes an equation to calculate cardiac output from the aortic pressure waveform which, in turn, is calculated from the brachial cuff pressure using neural network techniques, which is an algorithm very much dependent on the data set used to train it. In order to have a general neural network algorithm that can be applied to all populations, the training data needs to cover the complete range of possible brachial cuff pulses and corresponding aortic pulses. Pulses with all possible heart rates, shapes and pressure values need to be included in the training to have a general methodology.
The proposed invention methodology differs from the neural network in that it uses transfer functions based on harmonics ratio between the peripheral and central aortic waveforms where trends can be identified easily and consequently generalized to a larger population.
Even though harmonic amplification of waveforms along the arterial tree is well-established in cardiovascular hemodynamics, none of the prior art, except from the O'Rourke patent, addresses this significant issue. These methods don't show how changes in pressure pulse harmonics affect the calculated output. For example, a subjects' heart rate can vary considerably from one examination to another. This consequently alters the aortic pulses harmonics and affects the peripheral pulses harmonics. Any method that does not take heart rate and waveform morphology into account would fail in tests during drug intervention or any maneuvers that alter subject's pulse shape, pressure and heart rate, limiting the method's application and reducing its accuracy.
None of the prior art that uses the brachial cuff to sense a volume waveform addresses the fact that the volume waveform shape changes as cuff pressure changes in reference to the subject's blood pressure. Such changes would cause instability in all of these methods.
Also, these methods would introduce calibration-based errors because of the incorrect assumption that the oscillometric cuff volume waveform is a pressure pulse. None of these methods address this issue.